Bradykinin activates protein kinase C in cultured cortical collecting tubular cells.
Bradykinin activates protein kinase C in cultured cortical collecting tubular cells.
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缓激肽激活培养的皮质集合管细胞中的蛋白激酶 C。
DOI：
10.1152/ajprenal.1989.257.5.f808
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Anderson,RJ
中科院分区：
文献类型：
--
作者：
Dixon,BS;Breckon,R;Fortune,J;Sutherland,E;Simon,FR;Anderson,RJ
缓激肽抑制皮质集合管细胞中加压素刺激的水运输。通过对兔皮质集合管细胞进行原代培养，探讨了这种效应的生化机制。研究发现缓激肽可使细胞内储存的钙快速释放，增加 sn-1,2-二酰基甘油水平，并使膜结合蛋白激酶 C 活性增加五倍，这与兔皮质集合管细胞中磷脂酶 C 的刺激和蛋白激酶 C 的激活一致。此外，缓激肽对加压素刺激的腺苷 3',5'-环单磷酸 (cAMP) 形成产生 46% 的剂量依赖性抑制。用蛋白激酶 C 抑制剂 H-7 和十字孢菌素进行预处理，逆转了缓激肽介导的对加压素刺激的 cAMP 积累的抑制作用。相反，用磷脂酶 A2 抑制剂、mepacrine 或百日咳毒素进行预处理并不能阻止缓激肽对加压素刺激的 cAMP 产生的抑制作用，表明这种作用不是由前列腺素 E2 或百日咳毒素敏感鸟嘌呤核苷酸调节蛋白（例如 Gi）的激活介导的。因为缓激肽还抑制异丙肾上腺素刺激的 cAMP 形成，但不抑制基础毒素、毛喉毒素或霍乱毒素刺激的 cAMP 积累，因此这种抑制的位点似乎涉及激素受体或受体与刺激性鸟嘌呤核苷酸调节亚基 (Gs) 的偶联。结果表明，缓激肽刺激磷脂酶 C，导致蛋白激酶 C 激活，然后在激素受体水平抑制加压素刺激的 cAMP 产生，或在培养的皮质集合管细胞中抑制受体与 G 的偶联。
Bradykinin inhibits vasopressin-stimulated water transport in cortical collecting tubular cells. The biochemical mechanism of this effect was explored by means of primary cultures of rabbit cortical collecting tubular cells. Bradykinin was found to produce a rapid release of calcium from intracellular stores, an increase in sn-1,2-diacylglycerol levels, and a fivefold increase in membrane-bound protein kinase C activity, consistent with stimulation of phospholipase C and activation of protein kinase C in rabbit cortical collecting tubular cells. In addition, bradykinin produced a dose-dependent 46% inhibition of vasopressin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. Pretreatment with the protein kinase C inhibitors, H-7 and staurosporine, reversed the bradykinin-mediated inhibition of vasopressin-stimulated cAMP accumulation. In contrast, pretreatment with either the phospholipase A2 inhibitor, mepacrine, or pertussis toxin did not prevent the inhibitory effect of bradykinin on vasopressin-stimulated cAMP production, suggesting that the effects are not mediated by prostaglandin E2 or activation of a pertussis-toxin sensitive guanine nucleotide regulatory protein (e.g., Gi). Because bradykinin also inhibits isoproterenol-stimulated cAMP formation but does not inhibit either basal-, forskolin-, or cholera toxin-stimulated cAMP accumulation, the site of this inhibition appears to involve the hormone receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit (Gs). The results demonstrate that bradykinin stimulates phospholipase C leading to activation of protein kinase C, which then inhibits vasopressin-stimulated cAMP production at the level of the hormone receptor or coupling of the receptor to Gs in cultured cortical collecting tubular cells.